Timon Hussain1, Elamprakash N Savariar2, Julio A Diaz-Perez1, Karen Messer3, Minya Pu3, Roger Y Tsien2,4, Quyen T Nguyen1. 1. Division of Head and Neck Surgery, University of California San Diego, San Diego, California. 2. Department of Pharmacology, University of California San Diego, San Diego, California. 3. Division of Biostatistics, Moores Cancer Center, University of California San Diego, San Diego, California. 4. Howard Hughes Medical Institute, University of California San Diego, San Diego, California.
Abstract
BACKGROUND: We evaluated the use of intraoperative fluorescence guidance by enzymatically cleavable ratiometric activatable cell-penetrating peptide (RACPPPLGC(Me)AG) containing Cy5 as a fluorescent donor and Cy7 as a fluorescent acceptor for salivary gland cancer surgery in a mouse model. METHODS: Surgical resection of small parotid gland cancers in mice was performed with fluorescence guidance or white light (WL) imaging alone. Tumor identification accuracy, operating time, and tumor-free survival were compared. RESULTS: RACPP guidance aided tumor detection (positive histology in 90% [27/30] vs 48% [15/31] for WL; p < .001). An approximate 25% ratiometric signal increase as the threshold to distinguish between tumor and adjacent tissue, yielded >90% detection sensitivity and specificity. Operating time was reduced by 54% (p < .001), and tumor-free survival was increased with RACPP guidance (p = .025). CONCLUSION: RACPP provides real-time intraoperative guidance leading to improved survival. Ratiometric signal thresholds can be set according to desired detection accuracy levels for future RACPP applications.
BACKGROUND: We evaluated the use of intraoperative fluorescence guidance by enzymatically cleavable ratiometric activatable cell-penetrating peptide (RACPPPLGC(Me)AG) containing Cy5 as a fluorescent donor and Cy7 as a fluorescent acceptor for salivary gland cancer surgery in a mouse model. METHODS: Surgical resection of small parotid gland cancers in mice was performed with fluorescence guidance or white light (WL) imaging alone. Tumor identification accuracy, operating time, and tumor-free survival were compared. RESULTS:RACPP guidance aided tumor detection (positive histology in 90% [27/30] vs 48% [15/31] for WL; p < .001). An approximate 25% ratiometric signal increase as the threshold to distinguish between tumor and adjacent tissue, yielded >90% detection sensitivity and specificity. Operating time was reduced by 54% (p < .001), and tumor-free survival was increased with RACPP guidance (p = .025). CONCLUSION:RACPP provides real-time intraoperative guidance leading to improved survival. Ratiometric signal thresholds can be set according to desired detection accuracy levels for future RACPP applications.
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